Apolipoprotein E e4 allele influences aggressive behaviour in Alzheimer's disease

The rising number of people with cognitive impairment is placing health care budgets under significant strain. Dementia related behavioural change is a major independent risk factor for admission to expensive institutional care, and aggressive symptoms in particular are poorly tolerated by carers and frequently precipitate the collapse of home coping strategies. Aggressive change may result from known genetic risk factors for Alzheimer's disease (AD) and therefore accompany conventional markers such as apolipoprotein E (ApoE). We tested this hypothesis in 400 moderately to severely affected AD patients who were phenotyped for the presence of aggressive or agitated behaviour during the month prior to interview using the Neuropsychiatric Inventory with Caregiver Distress. The proportion of subjects with aggression/agitation in the month prior to interview was 51.8%. A significantly higher frequency of the e4 allele was found in individuals recording aggression/agitation in the month prior to interview (chi2 = 6.69, df = 2, p = 0.03). The additional risk for aggression/agitation conferred by e4 was also noted when e4 genotypes were compared against non-e4 genotypes (chi2 = 5.45, df = 1, p = 0.02, OR = 1.60, confidence interval (CI) 1.06 to 2.43). These results indicate that advanced Alzheimer's disease patients are at greater risk of aggressive symptoms because of a genetic weakness in apolipoprotein E.

Low-frequency electrical response to microbial induced sulfide precipitation

We investigated the sensitivity of low-frequency electrical measurements to microbe-induced metal sulfide precipitation. Three identical sand-packed monitoring columns were used; a geochemical column, an electrical column and a control column. In the first experiment, continuous upward flow of nutrients and metals in solution was established in each column. Cells of Desulfovibrio vulgaris (D. vulgaris) were injected into the center of the geochemical and electrical columns. Geochemical sampling and post-experiment destructive analysis showed that microbial induced sulfate reduction led to metal precipitation on bacteria cells, forming motile biominerals. Precipitation initially occurred in the injection zone, followed by chemotactic migration of D. vulgaris and ultimate accumulation around the nutrient source at the column base. Results from this experiment conducted with metals show (1) polarization anomalies, up to 14 mrad, develop at the bacteria injection and final accumulation areas, (2) the onset of polarization increase occurs concurrently with the onset of lactate consumption, (3) polarization profiles are similar to calculated profiles of the rate of lactate consumption, and (4) temporal changes in polarization and conduction correlate with a geometrical rearrangement of metal-coated bacterial cells. In a second experiment, the same biogeochemical conditions were established except that no metals were added to the flow solution. Polarization anomalies were absent when the experiment was replicated without metals in solution. We therefore attribute the polarization increase observed in the first experiment to a metal-fluid interfacial mechanism that develops as metal sulfides precipitate onto microbial cells and form biominerals. Temporal changes in polarization and conductivity reflect changes in (1) the amount of metal-fluid interfacial area, and (2) the amount of electronic conduction resulting from microbial growth, chemotactic movement and final coagulation. This polarization is correlated with the rate of microbial activity inferred from the lactate concentration gradient, probably via a common total metal surface area effect.

Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases.

Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past twenty years that the molecular events that precipitate disease have begun to be understood. Protein aggregation is a common feature of many neurodegenerative diseases, and it is assumed that the aggregation process plays a central role in pathogenesis. In this process, one molecule (monomer) of a soluble protein interacts with other monomers of the same protein to form dimers, oligomers, and polymers. Conformation changes in three-dimensional structure of the protein, especially the formation of beta-strands, often accompany the process. Eventually, as the size of the aggregates increases, they may precipitate as insoluble amyloid fibrils, in which the structure is stabilized by the beta-strands interacting within a beta-sheet. In this review, we discuss this theme as it relates to the two most common neurodegenerative conditions-Alzheimer's and Parkinson's diseases.

A structural and electrochemical investigation of 1-alkyl-3-methylimidazollum salts of the nitratodioxouranate(VI) anions [{UO2(NO3)(2)}(2)(mu(4)-C2O4)](2-), [UO2(NO3)(3)](-), and [UO2(NO3)(4)](2-)

The properties of the 1-butyl-3-methylimidazolium salt of the dinuclear mu(4)-(O,O,O',O'-ethane-1,2-dioato)bis[bis-(nitrato-O,O)dioxouranate(VI)] anion have been investigated using electrochemistry, single-crystal X-ray crystallography, and extended X-ray absorbance fine structure spectroscopy: the anion structures from these last two techniques are in excellent agreement with each other. Electrochemical reduction of the complex leads to the a two-electron metal-centered reduction of U(VI) to U(IV), and the production Of UO2, or a complex containing UO2. Under normal conditions, this leads to the coating of the electrode with a passivating film. The presence of volatile organic compounds in the ionic liquids 1-alkyl-3-methylimidazolium nitrate (where the 1-alkyl chain was methyl, ethyl, propyl, butyl, pentyl, hexyl, dodecyl, hexadecyl, or octadecyl) during the oxidative dissolution of uranium(IV) oxide led to the formation of a yellow precipitate. To understand the effect of the cation upon the composition and structure of the precipitates, 1-alkyl-3-methylimidazolium salts of a number of nitratodioxouranate(VI) complexes were synthesized and then analyzed using X-ray crystallography. It was demonstrated that the length of the 1-alkyl chain played an important role, not only in the composition of the complex salt, but also in the synthesis of dinuclear anions containing the bridging mu(4)-(O,O,O',O'-ethane-1,2-dioato), or oxalato, ligand, by protecting it from further oxidation.

Phase transformations in maraging steels

Research on the kinetics of precipitate formation and austenite reversion in maraging steels has received great attention due to their importance to steel properties. Judging from the literature in recent years, research into maraging steels has been very active, mainly extending to new types of steels, for new applications beyond the traditional strength requirements. This chapter provides an in-depth overview of the literature in this area. In addition, the kinetics of precipitate formation are analysed using the Johnson–Mehl–Avrami (JMA) theory.

Domain annihilation due to temperature and thickness gradients in single-crystal BaTiO3

The manner in which 90? ferroelectric-ferroelastic domains respond to changes in temperature has been mapped in BaTiO3 single crystals using atomic force microscopy. Domain periodicity remains unaltered until approximately 2 ? C below the Curie temperature (TC ), whereupon domains coarsened dramatically. This behavior was successfully rationalized by considering the temperature dependence of the parameters associated with standard models of ferroelastic domain formation. However, while successful in describing the expected radical increase in equilibrium period with temperature, the model did not predict the unusual mechanism by which domain coarsening occurred; this was not continuous at a local level but instead involved discrete domain annihilation events. Subsequent insights from a combination of free energy analysis for the system and further experimental data from an analogous situation, in which domain period increases with increasing crystal thickness, suggested that domain annihilation is inevitable whenever a component of the relevant gradient that affects domain period is orientated parallel to the domain walls. Consistent with this thesis, we note that, for the observations presented herein, the thermal gradient possessed a significant component parallel to the domain walls. We suggest that domain annihilation is a general feature of domain structures in gradient fields.

Characterisation of protein stability in rod-insert vaginal rings

A major goal in vaccine development is elimination of the ‘cold chain’, the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 oC, but not when stored at 40 oC / 75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 oC / 75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation as compared to the original formulation when stored at 40 oC /75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general.

Effect of Carbon Reduction on the Toughness of 9CrWVTaN Steels

Nitride-strengthened, reduced activation, martensitic steel is anticipated to have higher creep strength because of the remarkable thermal stability of nitrides. Two nitride-strengthened, reduced activation martensitic steels with different carbon contents were prepared to investigate the microstructure and mechanical property changes with decreasing carbon content. It has been found that both steels had the microstructure of full martensite with fine nitrides dispersed homogeneously in the matrix and displayed extremely high strength but poor toughness. Compared with the steel with low carbon content (0.005 pct in wt pct), the steel with high carbon content (0.012 pct in wt pct) had not only the higher strength but also the higher impact toughness and grain coarsening temperature, which was related to the carbon content. On the one hand, carbon reduction led to Ta-rich inclusions; on the other hand, the grain grew larger when normalized at high temperature because of the absence of Ta carbonitrides, which would decrease impact toughness. The complicated Al2O3 inclusions in the two steels have been revealed to be responsible for the initiated cleavage fracture by acting as the critical cracks.